About 8 million people in the United States suffer from a myocardial infarction (MI) during their lifetime, with about 800,000 new cases occurring each year. Despite the prevalence of MIs, however, conventional therapies remain limited by the inability of the myocardium to regenerate after injury and the shortage of donor organs that are available for transplantation. Indeed, the lack of effective therapies leads to more than 500,000 deaths per year in the United States alone and, although the use of reperfusion and pharmacological therapies have somewhat increased not only the rate of survival but also the quantity of salvaged tissue in MI patients, MI still continues to be a degenerative disease with a peak of cell death occurring at the onset of the infarction and also continuing thereafter. In this regard, it is thus thought that cell-based therapies or tissue engineering approaches could be two viable approaches to improve healing after a MI and restore the function of cardiac tissue.
With regard to cell-based therapies, it is appreciated that the myocardium includes, on average, 20 million cardiomyocytes per gram of tissue. Given that the weight of human left ventricle is about 400 g, an average ventricle thus consists of 4 billion cardiomyocytes. Heart failure, however, can affect about 25% of the left ventricle, which indicates that roughly 1 billion cardiomyocytes will need replacement. As such, cell therapy approaches involving the transplantation of suspensions of a number of autologous stem cells or progenitors into the damaged myocardium have been tested in preclinical studies or early clinical studies. So far though, the cells have only been transplanted into the heart via intracoronary infusion or intramyocardial injection, and cell engraftment is usually only about 0.1-5% of the transplanted cells and the percentage of the cells that eventually differentiate into the desired types is quite low. Moreover, single-dose transfer of a single cell type into a damaged tissue environment has not been sufficient to regenerate a complex tissue such as the heart. For these reasons, cell therapy alone has only met with marginal success and has been plagued by poor cell retention, survival rates, engraftment, and differentiation, such that it is often considered a secondary solution to repairing and regenerating damaged cardiac tissue.
With regard to tissue engineering approaches, a goal of tissue engineering is to use a combination of cells, engineered materials, and suitable biochemical and physical cues to restore, maintain, improve, or replace biological functions of damaged tissues or organs. In this regard, tissue engineering methods are being developed for cardiac repair as the methods provide the advantage of: (i) having the tissue constructs developed ex vivo to replace scar tissue; (ii) being able to control cell retention by making use of scaffolding materials; and (iii) being able to engineer heart tissue under precise and controllable conditions. Nevertheless, success of human myocardial tissue engineering for cardiac repair has still been limited by incompatibility with recapitulating native cardiac structural features, mismatch of structural and mechanical properties between scaffolds and native myocardial tissue, and poor survival after transplantation.